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Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

Authors
  • Salvador-Martín, Sara1
  • Raposo-Gutiérrez, Irene1
  • Navas-López, Víctor Manuel
  • Gallego-Fernández, Carmen
  • Moreno-Álvarez, Ana2
  • Solar-Boga, Alfonso2
  • Muñoz-Codoceo, Rosana
  • Magallares, Lorena3
  • Martínez-Ojinaga, Eva3
  • Fobelo, María J.
  • Millán-Jiménez, Antonio
  • Rodriguez-Martinez, Alejandro
  • Vayo, Concepción A.
  • Sánchez, Cesar4
  • Tolin, Mar4
  • Bossacoma, Ferrán
  • Pujol-Muncunill, Gemma
  • González de Caldas, Rafael
  • Loverdos, Inés
  • Blanca-García, José A.
  • And 6 more
  • 1 (M.S.-S.)
  • 2 (A.S.-B.)
  • 3 (E.M.-O.)
  • 4 (M.T.)
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
May 09, 2020
Volume
21
Issue
9
Identifiers
DOI: 10.3390/ijms21093364
PMID: 32397546
PMCID: PMC7247673
Source
PubMed Central
Keywords
License
Green

Abstract

Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders ( n = 27) and non-responders to anti-TNF therapy ( n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders ( p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.

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